Emergence of aztreonam/avibactam and tigecycline-resistant Pseudomonas putida group Co-producing blaIMP-1, blaAFM-4 and blaOXA-1041 with a novel sequence type ST268 in Southwestern China.

OBJECTIVES: The emergence of carbapenem-resistant Pseudomonas putida (CRPP) has raised public awareness. This study investigated two strains from the Pseudomonas putida group that were resistant to carbapenem, tigecycline, and aztreonam-avibactam (ATM-AVI), with a focus on their microbial and genomic characteristics. METHODS: We assessed the antibiotic resistance profile using broth dilution, disk diffusion, and E-test methods. Efflux pump phenotype testing and real-time quantitative PCR were employed to evaluate efflux pump activity in tigecycline resistance, while polymerase chain reaction was utilized to detect common carbapenem genes. Additionally, whole-genome sequencing was performed to analyze genomic characteristics. The transferability of blaIMP-1 and blaAFM-4 was assessed through a conjugation experiment. Furthermore, growth kinetics and biofilm formation were examined using growth curves and crystal violet staining. RESULTS: Both strains demonstrated resistance to carbapenem, tigecycline, and ATM-AVI. Notably, NMP can restore sensitivity to tigecycline. Subsequent analysis revealed that they co-produced blaIMP-1, blaAFM-4, tmexCD-toprJ, and blaOXA-1041, belonging to a novel sequence type ST268. Although they were closely related on the phylogenetic tree, they exhibited different levels of virulence. Genetic environment analysis indicated variations compared to prior studies, particularly regarding the blaIMP-1 and blaAFM-4 genes, which showed limited horizontal transferability. Moreover, it was observed that temperature exerted a specific influence on their biological factors. CONCLUSION: We initially identified two P. putida ST268 strains co-producing blaIMP-1, blaAFM-4, blaOXA-1041, and tmexCD-toprJ. The resistance to tigecycline and ATM-AVI can be attributed to the presence of multiple drug resistance determinants. These findings underscore the significance of P. putida as a reservoir for novel antibiotic resistance genes. Therefore, it is imperative to develop alternative antibiotic therapies and establish effective monitoring of bacterial resistance.

Febuxostat Protects Human Aortic Valve Endothelial Cells From Oxidized Low-density Lipoprotein-Induced Injury and Monocyte Attachment.

ABSTRACT: Atherosclerosis (AS) is a common cardiovascular disease with high morbidity and mortality. The pathogenesis of AS is closely related to endothelial dysfunction, which is mainly induced by oxidative stress, inflammation, and enhanced adhesion of monocytes to endothelial cells on the vessel wall. Febuxostat is a novel antigout agent recently reported to exert protective effects on endothelial dysfunction. This study aims to investigate the protective capacity of febuxostat against oxidized low-density lipoprotein (ox-LDL)-induced injury and monocyte attachment to endothelial cells. Human aortic valve endothelial cells (HAVECs) were stimulated with ox-LDL in the presence or absence of febuxostat (5 and 10 µM) for 6 hours. Mitochondrial reactive oxygen species were measured using MitoSox red staining, and the level of protein carbonyl was detected using enzyme-linked immunosorbent assay (ELISA). The expressions of IL-6, TNF-α, tissue factor (TF), VCAM-1, and ICAM-1 were evaluated with qRT-PCR assay and ELISA. Calcein-AM staining was used to determine the attachment of U937 monocytes to HAVECs. quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot were used to measure the expression level of early growth response 1 (Egr-1) in HAVECs. First, the elevated expression of LOX-1, activated oxidative stress, excessive secreted inflammatory factors, and promoted expression of TF induced by stimulation with ox-LDL were significantly reversed by febuxostat, indicating a protective effect of febuxostat against endothelial dysfunction. Second, the upregulated VCAM-1 and ICAM-1, as well as the increased proportion of adhered monocytes to HAVECs induced by ox-LDL, were significantly alleviated by febuxostat. Finally, the promoted expression level of Egr-1 induced by ox-LDL was pronouncedly suppressed by febuxostat. We conclude that febuxostat protected HAVECs from ox-LDL-induced injury and monocyte attachment.

CoO Nanoparticles Combined with MRI: Analysis of No-Reflow in Patients with Acute ST-Segment Elevation Myocardial Infarction after PCI and the Effect of Coronary Nicorandil.

Magnetic resonance imaging (MRI) has become one of the most important medical imaging techniques in the clinic due to its high degree of soft tissue resolution and no radiation damage, and it plays an important role in the early diagnosis and treatment of tumors. This article mainly studies the analysis of no-reflow in patients with acute ST-segment elevation myocardial infarction after PCI and the effect of coronary nicorandil on CoO nanoparticles combined with MRI. In this paper, the synthesized water-soluble nanoparticles are dispersed in a 2% xanthan gum or agarose solution. In an MRI analyzer, the T1 value is tested with the inversion recovery sequence, and the T2 value is tested with the hard pulse CPMG sequence. The gyroscope imaging sequence performs T1-weighted and T2-weighted imaging tests. Calculated densitometry (QCA) was used to measure the stenosis of the coronary lesions, the length of the lesions and the diameter of the lumen before stent implantation. In order to facilitate the collection of urine samples, this article adopts the method of inserting a catheter to drain the patient for sampling. From the baseline state at the time of enrollment to 150 minutes after PCI, polyethylene containing 0.1% butylated hydroxyanisole is used. Urine samples were taken from the test tube every 30 minutes, a total of 6 times were collected, and the collected urine samples were stored in a low-temperature refrigerator at -80℃ for the final inspection. This paper uses calculation software to calculate the risk of death and death/myocardial infarction in the hospital and at 6 months after discharge. The data showed that the postoperatively detected CKMB and cTnI were higher than those before the operation, but the peak value of the nicorandil group was lower than that of the control group, but there was still no statistical difference (P>0.05). The results show that nicorandil can significantly improve the no-reflow phenomenon in AMI patients during PCI.

Diffusion tensor imaging revealed different pathological processes of white matter hyperintensities.

BACKGROUND: Although increasing evidence showed the correlations between white matter hyperintensities (WMHs) and cognitive impairment, the relationship between them is still modest. Many researchers began to focus on the variation caused by the heterogeneity of WMH. We tried to explore the pathological heterogeneity in WMH by using diffusion tensor imaging (DTI), so as to provide a new insight into the future research. METHODS: Diffusion weighted images (DWIs) of the brain were acquired from 73 patients with WMH and 18 healthy controls, which were then modeled by DTI. We measured fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of white matter of the periventricular frontal lobe (pFL), periventricular occipital lobe (pOL), periventricular parietal lobe (pPL) and deep centrum ovales (dCO), and grouped these measures according to the Fazekas scale. Then we compared the DTI metrics of different regions with the same Fazekas scale grade. RESULTS: Significantly lower FA values (all p < 0.001), and higher MD (all p < 0.001) and RD values (all p < 0.001) were associated with WMH observed in the periventricular frontal lobe (pFL) compared to all other regions with the same Fazekas grades. The AD of WMH in the pFL was higher than that of pPL and dCO, but the differences between groups was not as high as of MD and RD, as indicated by the effect size. In the normal control group, DTI metrics between pFL and other regions were not significantly different or less significant different. The difference of DTI metrics of WMH between pPL, pOL and dCO was lower than that of normal white matter, as indicated by the effect size. CONCLUSION: Distinct pathological processes can be revealed by DTI between frontal periventricular WMH and other regions. These processes may represent the effects of severe demyelination within the frontal periventricular WMH.

[Retracted] Rosuvastatin suppresses platelet­derived growth factor­BB­induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway.

[This retracts the article DOI: 10.3892/etm.2013.1265.].

Inhibiting stanniocalcin 2 reduces sunitinib resistance of Caki-1 renal cancer cells under hypoxia condition.

Background: Our previous study has suggested that blocking stanniocalcin 2 (STC2) could reduce sunitinib resistance in clear cell renal cell carcinoma (ccRCC) under normoxia. The hypoxia is a particularly important environment for RCC occurrence and development, as well as sunitinib resistance. The authors proposed that STC2 also plays important roles in RCC sunitinib resistance under hypoxia conditions. Methods: The ccRCC Caki-1 cells were treated within the hypoxia conditions. Real-time quantitative PCR and Western blotting were applied to detect the STC2 expression in ccRCC Caki-1 cells. STC2-neutralizing antibodies, STC2 siRNA, and the recombinant human STC2 (rhSTC2) were used to identify targeting regulation on STC2 in modulating sunitinib resistance, proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion. In addition, autophagy flux and the lysosomal acidic environment were investigated by Western blotting and fluorescence staining, and the accumulation of sunitinib in cells was observed with the addition of STC2-neutralizing antibodies and autophagy modulators. Results: Under hypoxia conditions, sunitinib disrupted the lysosomal acidic environment and accumulated in Caki-1 cells. Hypoxia-induced the STC2 mRNA and protein levels in Caki-1 cells. STC2-neutralizing antibodies and STC2 siRNA effectively aggravated sunitinib-reduced cell viability and proliferation, which were reversed by rhSTC2. In addition, sunitinib promoted EMT, migration, and invasion, which were reduced by STC2-neutralizing antibodies. Conclusion: Inhibiting STC2 could reduce the sunitinib resistance of ccRCC cells under hypoxia conditions.

Healthcare quality and safety assessment based on annual scorekeeping.

Objective: To explore the practice of medical quality and safety evaluation system based on annual score under the background of establishing modern hospital management system and strengthening national public hospital performance evaluation. Methods: Statistical analysis was used to study the improvement of medical quality and safety in hospitals after the implementation of score evaluation, and the existing problems were analyzed according to the actual situation and related requirements. Results: The hospital's medical quality and safety evaluation system ran smoothly, the evaluation indexes could be implemented, and the evaluation results were used properly. The improvement of hospital medical quality and operation efficiency has achieved good results. Conclusion: The evaluation system of medical quality and safety for physicians and medical technicians based on annual score can achieve the whole process, all-round, personalized and information-based evaluation, and promote the high-quality development of hospitals. It is necessary to further improve the range of evaluation and carry out the evaluation of the evaluation system by relevant personnel.

Safety of Bivalirudin Combined with Ticagrelor in the Emergency PCI in Patients with Acute ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: The present study aimed to investigate the application safety of bivalirudin combined with ticagrelor in the emergency percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: From October 1, 2018, to December 30, 2019, 210 patients with STEMI admitted to the Department of Cardiology who underwent emergency PCI were randomly divided into the bivalirudin group (group A, N = 105) and the unfractionated heparin group (group B, N = 105). Before the emergency PCI operation after admission, the loading dose of aspirin (300 mg) was given orally, and then 100 mg/d. At the same time, the loading dose of ticagrelor (180 mg) was administered orally, and then 90 mg/bid. The adverse events and the hemorrhage events 30 days after the operation were observed and recorded. RESULTS: There were five hemorrhage cases in the bivalirudin group, with one case of secondary hemorrhage and four cases of mild hemorrhage. There were 14 hemorrhages in the unfractionated heparin group with one case of secondary hemorrhage and thirteen cases of mild hemorrhage. In terms of mild hemorrhage, the hemorrhage rate in the bivalirudin group was significantly lower than that in the unfractionated heparin group (3.8% vs. 12.4%, P = 0.040). One patient died in the unfractionated heparin group, while no deaths occurred in the bivalirudin group during the thirty days of follow-up. No myocardial infarction, revascularization, or stroke occurred in the two groups within 30 days after the operation. CONCLUSION: Compared with unfractionated heparin combined with ticagrelor in patients with STEMI undergoing emergency PCI treatment, bivalirudin combined with ticagrelor could significantly reduce the occurrence of mild hemorrhage events, and it would not increase the incidence of MACE during the 30 days of follow-up.

The efficacy and safety of edoxaban versus warfarin in preventing clinical events in atrial fibrillation: A systematic review and meta-analysis.

Atrial fibrillation (AF) is the most common type of arrhythmia. Warfarin reduces the incidence and mortality of strokes in patients with AF. Edoxaban reduces the bleeding risk in patients with AF. This study evaluates the efficacy and safety of edoxaban versus warfarin in preventing clinical events in patients with AF through a meta-analysis of randomized controlled trials (RCTs). RCTs were retrieved from medical literature databases. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare the primary and safety endpoints. In total, five articles (10 trial comparisons) containing 24,836 patients were retrieved. Of these patients, 16,268 (65.5%) received edoxaban and 8,568 (34.5%) received warfarin. Compared with warfarin, edoxaban significantly reduced the incidence of cardiovascular death (CVD), major bleeding, and non-major bleeding (RR: 0.86, 95% CI: 0.80-0.93, I2 : 0.0%; RR: 0.65, 95% CI: 0.59-0.71, I2 : 75.6%; and RR: 0.80, 95% CI: 0.77-0.84, I2 : 79.3%, respectively). Edoxaban did not increase the incidence of stroke, systemic embolic events, myocardial infarction, and adverse events compared with warfarin (RR: 1.00, 95% CI: 0.90-1.11, I2 : 42.8%; RR: 1.00, 95% CI: 0.67-1.49, I2 : 0.0%; RR: 1.08, 95% CI: 0.93-1.27, I2 : 0.0%; RR: 1.00, 95% CI: 0.91-1.10, I2: 46.4%, respectively). This meta-analysis indicated that compared with warfarin, edoxaban can significantly reduce the incidence of CVD and major and non-major bleeding. The anticoagulant effect and safety of edoxaban may be better than those of warfarin.

Meta-analysis of Duration of Continuous Dual Antiplatelet Therapy and Late Stent Thrombosis After Second-Generation Drug Stent Implantation.

INTRODUCTION: The aim of the present study was to perform a systematic comparison of the incidence of late and extremely late stent thrombosis (ST) with short-term and long-term dual antiplatelet therapy (DAPT) after a second-generation drug-eluting stent (DES) implantation. METHODS: Randomized controlled trials using short-term and long-term DAPT and reporting late ST (30 days-1 year) and extremely late ST (longer than 1 year) after a percutaneous coronary intervention (PCI) with DES were searched and compared in the Life Sciences and Biomedical Information Bibliographic Database (MEDLINE), EMBASE, Cochrane Central, and ClinicalTrials.com. ST was used as the primary endpoint of the therapeutic outcome, and the fixed-effects model (I2 < 50%) or random-effects model (I2 ≥ 50%) was adopted for the combined analysis. The odds ratio (OR) and 95% confidence interval (CIs) were used to represent the results. P < 0.05 in the combined result indicated that the difference was statistically significant. RESULTS: A total of five randomized controlled trials consisting of 7142 patients were included, with 3556 cases of short-term DAPT (at most 6 months), and 3586 cases of long-term DAPT (at least 12 months). There was no significant difference between late ST and administration duration of DAPT (OR 0.98, 95% CI 0.30-3.18; P = 0.97, I2 = 0%). There was also no significant difference between the incidence of extremely late ST and the duration of DAPT application (OR 0.30, 95% CI 0.03-2.95; P = 0.31). CONCLUSION: The duration of continuous DAPT application had no effect on the occurrence of late and extremely late ST.

Latest Clinical Evidence About Effect of Acetylcysteine on Preventing Contrast-Induced Nephropathy in Patients Undergoing Angiography: A Meta-Analysis.

Contrast-induced nephropathy (CIN) is a serious complication of angiographic procedures. It is the third most common cause of hospital acquired acute renal injury. As there are currently no approved therapies for CIN, prevention could be the best strategy to address this issue. Acetylcysteine may indirectly play an antioxidant role by inducing the synthesis of glutathione. Acetylcysteine can also reduce renal vasoconstriction induced by contrast medium stimulation by stabilizing nitric oxide and acting directly or indirectly on renal cortex and medulla microcirculation. To evaluate the effect of acetylcysteine on the prevention of CIN in patients after angiography, we systematically searched and analyzed the clinical data of patients including the incidence of CIN and change in serum creatinine (SCr) at 48 hours after angiography from selected articles. The result showed that acetylcysteine significantly reduces the incidence of CIN (risk ratios: 0.78, 95% CI: 0.68-0.90, I2 = 37.3%) and the level of SCr (standardized mean difference: -0.53, 95% CI: -0.93 to -0.12, I2 = 91.5%) after angiography compared with the control group. Overall, the use of acetylcysteine in patients after angiography was associated with a significant reduction of CIN and the level of SCr.

Transfer of exosomal microRNA-203-3p from dendritic cells to bone marrow-derived macrophages reduces development of atherosclerosis by downregulating Ctss in mice.

Dendritic cell-derived exosomes have been proven to be efficient adjuvant options for anti-tumor vaccines in cancer immunotherapy. However, their potency in atherosclerosis remains unclear. Here we summarize the association of microRNA-203-3p (miR-203-3p) with dendritic cell-derived exosomes and atherosclerosis. Firstly, dendritic cell-derived exosomes and bone marrow-derived macrophages were isolated, after which expression of miR-203-3p and cathepsin S was determined. After the establishment of atherosclerosis mouse models, gain- and loss-of-function experiments were conducted for the analysis of effects of miR-203-3p and cathepsin S on foam-cell formation, lipid accumulation, collagen deposition and serum total cholesterol. The results found high expression of cathepsin S in atherosclerosis mice and downregulation of miR-203-3p in the serum of atherosclerosis patients and ox-LDL-simulated bone marrow-derived macrophages. Cathepsin S was the target gene of miR-203-3p. miR-203-3p transporting from exosomes to bone marrow-derived macrophages resulted in inhibition of cathepsin S expression and atherosclerosis-related phenotypes in bone marrow-derived macrophages, thus alleviating atherosclerosis in mice, and this process was found to involve the p38/MAPK signaling pathway. These findings provided evidence that the transfer of miR-203-3p by dendritic cell-derived exosomes targeted cathepsin S in bone marrow-derived macrophages to attenuate atherosclerosis progression in mice, serving as a promising clinical target for atherosclerosis.

The Efficacy And Safety Of Aspirin As The Primary Prevention Of Cardiovascular Disease: An Updated Meta-Analysis.

PURPOSE: Information regarding the use of aspirin for patients with no known cardiovascular disease remains conflicting. We performed an updated meta-analysis to evaluate the efficacy and safety of aspirin for primary prevention of cardiovascular disease. PATIENTS AND METHODS: PubMed, MEDLINE, and Cochrane library databases were searched for randomized controlled trials comparing aspirin with placebos or no treatment published up until November 1, 2018. The primary efficacy endpoint was all-cause death. The secondary endpoints included cardiovascular death, myocardial infarction, and stroke. The safety endpoints included major bleeding, gastrointestinal bleeding, and hemorrhagic stroke. RESULTS: Fourteen studies were included. Aspirin use was associated with a lower risk of myocardial infarction than placebo use or no treatment (risk ratio [RR], 0.83, 95% confidence interval [CI]: 0.73-0.95, P = 0.005). Additionally, compared with the control groups, aspirin use was not associated with a lower risk of all-cause mortality or cardiovascular mortality. In terms of safety, aspirin use was associated with a higher risk of major bleeding (RR, 1.40, 95% CI: 1.25-1.57, P = 0.000), gastrointestinal bleeding (RR, 1.58, 95% CI: 1.25-1.99, P = 0.000), and hemorrhagic stroke (RR, 1.30, 95% CI: 1.06-1.60, P = 0.011). Furthermore, the treatment effect was not significantly modified by patients' clinical characteristics. No publication bias was present. CONCLUSION: Aspirin use reduced the myocardial infarction risk in patients without known cardiovascular disease, but had no effect in terms of reducing the risk of all-cause death, cardiovascular death, and stroke, and increased the risk of major bleeding, gastrointestinal bleeding, and hemorrhagic stroke.

Thrombus aspiration catheter improve the myocardial reperfusion of STEMI patients with high thrombus load during the emergency PCI operation.

OBJECTIVE: This study aims to discuss the efficacy and safety of the application of thrombus aspiration catheters during emergency PCI operations for acute ST-elevation myocardial infarction (STEMI) patients with high thrombus load. METHODS: A total of 204 patients diagnosed with acute STEMI and high thrombus load in the Sixth Affiliated Hospital of Guangxi Medical University from July 1, 2016 to June 30, 2017 were selected for the present study. These patients were randomly divided into two groups: thrombus catheter aspiration group (group A, n = 101), and balloon dilatation group (group B, n = 103). The blood flow of the culprit coronary artery in the thrombolysis in myocardial infarction (TIMI) immediately after the emergency PCI operation in these two groups of patients was recorded. Then, an echocardiogram was performed to determine the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) after the operation, and data on major adverse cardiovascular events (MACE) during the 30 days of postoperative follow-up were collected. RESULTS: The comparative difference between these two groups of patients in terms of hypertension, smoking, diabetes, usage rate of GPIIb/IIIa receptor antagonist, time from hospitalization to balloon dilatation (D2B) and other basic clinical data was not statistically significant (P > 0.05). The postoperative TIMI flow grade of these two groups of patients improved, and the comparative difference between the data obtained from these two groups was statistically significant (P < 0.05). The comparative difference between these two groups in terms of LVEDD and LVEF at 7 days after the operation was not statistically significant (P > 0.05). There was a difference in the occurrence rate of MACE in these two groups of patients during the 30 days of postoperative follow-up, but the comparative difference between these two groups was not statistically significant (P = 0.335). CONCLUSION: The application of thrombus aspiration catheter during the emergency PCI operation of STEMI patients with high thrombus load can better improve the myocardial reperfusion. There is no basis for increasing the stroke occurrence risk. However, it obviously fails to improve the recent prognosis and more studies need to explore its effect on myocardial remodeling and major adverse cardiovascular events.

Value of the expression of miR-208, miR-494, miR-499 and miR-1303 in early diagnosis of acute myocardial infarction.

AIMS: This study aims to investigate the value of the expression of miR-208, miR-494, miR-499 and miR-1303 in the early diagnosis of acute myocardial infarction (AMI). MAIN METHODS: Patients were divided into two groups: AMI group (n = 41), and Stable angina pectoris (SAP) group (n = 32). Peripheral venous blood was sampled from these patients at the time of admission (T0), 6 h after onset (T6) and 12 h after onset (T12), while blood was sampled once from healthy subjects who underwent physical examination in the same time period (control group, n = 10). The expression of miR-208, miR-494, miR-499 and miR-1303 in serum were detected by real-time quantitative polymerase chain reaction (qRT-PCR), and differences in miRNA expression among these three groups of patients were analyzed. KEY FINDINGS: Serum miR-208, miR-494, miR-499 and miR-1303 expression levels at different time points were significantly higher in the AMI group than in the SAP group and control group. The differences among these groups were statistically significant (P < 0.05), while the difference between the SAP group and control group was not statistically significant (P > 0.05). Variation trend: The miRNA levels above began to increase at T0 in the AMI group, the peak levels of miR-208, miR-494 and miR-499 appeared before T12, and the peak level of miR-1303 appeared between T6 and T12, or after T12. SIGNIFICANCE: miR-208, miR-494, miR-499 and miR-1303 were not superior to hs-cTnI as myocardial markers in the diagnosis of early acute myocardial infarction.

Rosuvastatin may reduce the incidence of cardiovascular events in patients with acute coronary syndromes receiving percutaneous coronary intervention by suppressing miR-155/SHIP-1 signaling pathway.

PURPOSE: The beneficial effect of rosuvastatin against percutaneous coronary intervention (PCI) related procedural myocardial injury has been determined mostly in patients with acute coronary syndromes (ACS). However, the detailed therapeutic mechanism has not been well studied. METHODS: Patients with ACS receiving PCI (n = 159) were randomized to control group (placebo treatment) or to rosuvastatin group (20 mg 12 h before PCI, and a further 20 mg 2 h preprocedure dose). Levels of INF-γ, TNF-α, IL-6, miR-155/SHIP-1, and CD4(+)FoxP3(+)Treg in peripheral blood were detected before PCI and 24 h after PCI. Clinical data of these patients were also collected in this prospective study. RESULTS: Compared with placebo, rosuvastatin treatment significantly reduced the incidence of periprocedural myocardial infarction (PMI) and levels of cardiac troponin I (cTnI) associated with decreased relative expression of serum miR-155, levels of inflammatory cytokines (INF-γ, TNF-α, and IL-6), increased SHIP-1 expression and CD4(+)FoxP3(+)Treg percentage values (P < 0.05). In addition, patients with rosuvastatin pretreatment also reduced incidence of 30 days major adverse cardiac events (MACE) compared to the patients with placebo treatment (16 patients vs. 28 patients, P = 0.038). CONCLUSIONS: Our study suggests that high loading dose rosuvastatin pretreatment may reduce the incidence of cardiovascular events and levels of inflammatory markers in patients with ACS receiving PCI, which may be explained at least in part, by mechanism involving suppression of miR-155/SHIP-1 signaling pathway.

Rosuvastatin suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway.

An imbalance in the proliferation and migration of vascular smooth muscle cells (VSMCs) is significant in the onset and progression of vascular diseases, including arteriosclerosis and restenosis subsequent to vein grafting or coronary intervention. Rosuvastatin, a selective inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, has pharmacological properties including the ability to reduce low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (VLDL-C) levels, slow atherosclerosis progression and improve coronary heart disease outcomes. However, little is known concerning the molecular mechanism by which rosuvastatin affects vascular cell dynamics. In this study, we studied the inhibitory role of rosuvastatin on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, as well as the molecular mechanisms involved. MTT data showed that rosuvastatin markedly inhibited the proliferation of PDGF-BB-induced VSMCs in a time-dependent manner. VSMCs are able to dedifferentiate into a proliferative phenotype in response to PDGF-BB stimulation; however, rosuvastatin effectively attenuated this phenotype switching. Moreover, we also showed that rosuvastatin significantly suppressed PDGF-BB-induced VSMC migration, which may be a result of its inhibitory effect on the protein expression of matrix metalloproteinase-2 (MMP2) and MMP9. Investigation into the molecular mechanisms involved revealed that rosuvastatin inhibited the mitogen-activated protein kinase (MAPK) signaling pathway by downregulating extracellular signal-regulated kinase (ERK) and p38 MAPK, although the phosphorylation level of c-Jun N-terminal kinase (c-JNK) was not altered following rosuvastatin treatment. In conclusion, the present study showed that rosuvastatin suppressed PDGF-BB-induced VSMC proliferation and migration, indicating that rosuvastatin has the potential to become a promising therapeutic agent for the treatment of atherosclerosis and restenosis.